Pathophysiology, diagnosis, and treatment of gastrointestinal stromal tumors

Abstract

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Activating mutations of KIT or the platelet-derived growth factor receptor alpha gene (PDGFRA) have been identified in the vast majority of GISTs. The respective oncoproteins exhibit constitutive tyrosine kinase activity and promote cell growth. KIT and PDGFRA mutations are rarely found in GISTs in patients with neurofibromatosis type 1 (NF1) suggesting that the pathogenesis of GIST in NF1 patients is different from that in non-NF1 patients. Endoscopic diagnosis of GIST is usually difficult. Endoscopic ultrasonography (EUS)-guided fine-needle aspiration biopsy (EUS-FNAB) is a useful method for the diagnosis of GIST and for the detection of KIT or PDGFRA mutations. Imatinib mesylate, a tyrosine kinase inhibitor known to inhibit the activities of BCR-ABL, KIT, and PDGFR, is currently being used for the treatment of both chronic myeloid leukemia and metastatic GIST. The clinical response to imatinib therapy correlates with the types of mutations of KIT and PDGFRA, and the determination of KIT and PDGFRA mutations is useful for predicting the effect of imatinib. Resistance to imatinib after an initial response has been reported; secondary point mutations in KIT or PDGFRA that confer imatinib resistance are the most common mechanisms responsible for acquired resistance to imatinib. The continued development of target-specific therapies should increase the probability of cure in most patients with GISTs.

Expressão do P16 e do PDGFR-Beta no adenocarcinoma gástrico

“…Although there is not a close relation between both markers, it could be speculated that overexpression of PDGFR-beta in cancer cells, increasing mitogenic stimuli to cell could be associated to loss of activity of p16, which is one of the important cell cycle inhibitors. Besides, promising results in treatment of these patients with tyrosine kinase inhibitors, such as imatinib (former known as STI571, Gleevec, Novartis Pharmaceutical Corp, East Hanover, NJ, USA) have been reported for gastrointestinal stromal tumours (GISTs) in which PDGFR is overexpressed 13,15,20,21 . In a gastric carcinoma animal model, it was demonstrated increase in antitumour and cytotoxic effects of 5-FU and paclitaxel when combined with imatinib 22 .…”

Hemorragia digestiva provocada por tumor estromal gastrointestinal avançado de duodeno

“…possuem grande potencial maligno 1,3,4,7,8 . Os índices elevados de recorrência desta doença após o tratamento exclusivamente cirúrgico foram responsáveis pelo desenvolvimento de novas modalidades de tratamento adjuvante, sendo atualmente o mesilato de imatinib o agente mais estudado.…”

Gastrointestinal Stromal Tumor of the Stomach Presenting as a Perigastric Abscess

“…1 GIST의 낭성 변화는 종양의 크기가 큰 경우 출혈 혹은 괴사에 뒤따라 나타날 수 있다. 2 그러나 위에 발생한 GIST 가 복강 내 농양의 양상으로 발견된 증례는 드물게 보고되었 고, [3][4][5][6][7] 농양 발생의 위험인자로는 궤양, 누공, 종양의 괴사 등이 있다.…”